Acetic Acid → HCID 58542013, compound

HRID 1966760Notes

Reaction equation

HRID 1966760 reaction equation
[C:1]([OH:4])(=O)[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C.[NH2:36][C:37]1[N:42]=[CH:41][C:40]([C:43]2[CH:66]=[CH:65][C:46]3[N:47]([C:61]([CH3:64])([CH3:63])[CH3:62])[C:48]([C:50]4[CH:59]=[C:58]([F:60])[CH:57]=[CH:56][C:51]=4[C:52]([NH:54]O)=[NH:53])=[N:49][C:45]=3[CH:44]=2)=[CH:39][N:38]=1>CN(C=O)C>[C:61]([N:47]1[C:46]2[CH:65]=[CH:66][C:43]([C:40]3[CH:41]=[N:42][C:37]([NH2:36])=[N:38][CH:39]=3)=[CH:44][C:45]=2[N:49]=[C:48]1[C:50]1[CH:59]=[C:58]([F:60])[CH:57]=[CH:56][C:51]=1[C:52]1[N:54]=[C:1]([CH3:2])[O:4][N:53]=1)([CH3:64])([CH3:62])[CH3:63]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178448435HCID 178448435, compound

Product 1

HCID 58542013HCID 58542013, compoundYield 13.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of acetic acid (52 mg, 0.86 mmol) and HATU (326 mg, 0.86 mmol) in DMF (4 mL) is added triethylamine (0.12 mL, 0.86 mmol). The reaction mixture is stirred at room temperature for 10 minutes and 2-[5-(2-amino-pyrimidin-5-yl)-1-tert-butyl-1H-benzimidazol-2-yl]-4-fluoro-N-hydroxy-benzamidine (300 mg, 0.72 mmol) is added. The reaction mixture is stirred at room temperature for 2 hours then warmed to 80° C. and stirred for 15 hours. The reaction mixture is cooled to room temperature and concentrated in vacuo. EtOAc (30 mL) is added and the organics washed sequentially with saturated NaHCO3 solution (30 mL) and H2O (30 mL) then dried (Na2SO4), filtered and concentrated. Purification via flash chromatography (10 g silica gel, 1.5-3% MeOH/CH2Cl2) affords the title compound (43 mg, 10%). LCMS (ESMS): m/z 444.32 (M++1)

Workup

  1. stirringThe reaction mixture is stirred at room temperature for 2 hours
  2. temperaturethen warmed to 80° C.
  3. stirringstirred for 15 hours
  4. temperatureThe reaction mixture is cooled to room temperature
  5. concentrationconcentrated in vacuo
  6. additionEtOAc (30 mL) is added
  7. washthe organics washed sequentially with saturated NaHCO3 solution (30 mL) and H2O (30 mL)
  8. dry with materialthen dried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customPurification via flash chromatography (10 g silica gel, 1.5-3% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-388fb288b73547528b260e5e23c5f564
Source dataset
uspto-grants-2013_04
Patent number
US08420655B2

Reaction notes

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